Cardiovascular disease such as acute myocardial infarction (AMI) is a major cause of death in industrial countries. Concerning AMI, Reperfusion therapy immediately after onset of AMI has been shown to limit infarct size and preserve cardiac function. However, successful reperfusion determined by coronary angiography is not always accompanied by adequate reperfusion at the heart tissue level and improvement of cardiac dysfunction and injury in the chronic phase after AMI. Therefore, it is reasonable to develop a promising adjunctive therapy in patients with AMI.
Obesity-linked complications including type 2 diabetes, dyslipidemia and hypertension have been shown to predict severity and outcome of AMI. It has also been shown that obesity-related diseases are associated with increased cardiac damage and impaired left ventricular functions after successful percutaneous coronary intervention (PCI) for AMI.
Adiponectin is an adipose-derived hormone, which plays a protective role in the development of obesity-linked disorders. In clinical studies, plasma adiponectin levels are downregulated in association with cardiovascular risk factors including type 2 diabetes, hypertension, dyslipidemia and low-grade inflammations. Consistent with these clinical observations, a number of experimental studies show that adiponectin-deficiency contributes to diet-induced insulin resistance, salt-sensitive hypertension and impaired ischemia-induced neovascularization. Recently, several mouse studies demonstrated adiponectin has beneficial effects on the heart under pathological conditions. Adiponectin deficient (APN-KO) mice exhibit enhanced concentric cardiac hypertrophy after pressure overload (Nat Med. 2004 10(12), P. 1384-1389, Cardiovasc Res. 2005 67(4), P. 705-713). It has been shown that adiponectin inhibits the development of severe myocarditis in leptin-deficient ob/ob mice (J Int Med Res. 2005 33(2), P. 207-214). With regard to myocardial infarction, ablation of adiponectin in mice causes increased infarct size and adverse cardiac remodeling following myocardial ischemia-reperfusion (Nat Med. 2005 11(10), P. 1096-1103). Supplementation of adiponectin into wild type (WT) and APN-KO mice leads to diminished infarct size and improved cardiac function. Adiponectin also exerts favorable actions on systolic dysfunction in WT mice following permanent coronary ligation. Consistent with these experimental observations, high adiponectin levels were associated with improvement of cardiac damage and function after reperfusion therapy in patients with AMI (Am J Cardiol. 2008 101(12), P. 1712-1715). Thus, adiponectin protein may have clinical utility in the treatment of patients with AMI.